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Context: Each year the European Association of Urology (EAU) produce a document based on the most recent evidence on the diagnosis, therapy, and follow-up of testicular cancer (TC). Objective: To represent a summarised version of the EAU guidelines on TC for 2023 with a focus on key changes in the 2023 update. Evidence acquisition: A multidisciplinary panel of TC experts, comprising urologists, medical and radiation oncologists, and pathologists, reviewed the results from a structured literature search to compile the guidelines document. Each recommendation in the guidelines was assigned a strength rating. Evidence synthesis: For the 2023 EAU guidelines on TC, a review and restructure were undertaken. The key changes incorporated in the 2023 update include: new supporting text regarding venous thromboembolism prophylaxis in males with metastatic germ cell tumours receiving chemotherapy; quality of life after treatment; an update of the histological classifications and inclusion of the World Health Organization 2022 pathological classification; inclusion of the revalidation of the 1997 International Germ Cell Cancer Collaborative Group prognostic risk factors; and a new section covering oncology treatment protocols. Conclusions: The 2023 version of the EAU guidelines on TC include the highest available scientific evidence to standardise the management of TC. Better stratification and optimisation of treatment modalities will continue to improve the high survival rates for patients with TC. Patient summary: This article presents a summary of the European Association of Urology guidelines on testicular cancer published in 2023 and includes the latest recommendations for management of this disease. The guidelines are a valuable resource that may help patients in understanding treatment recommendations.

To (i) identify a novel risk stratification for patients complaining of haemospermia; and, (ii) compare its predictive ability to select high-risk patients by retrospectively validating the EAU guidelines classification.Data from 283 consecutive patients complaining of a single episode/recurrent haemospermia were retrospectively analyzed. Patients were stratified into low vs high-risk according to EAU guidelines, whose diagnostic performance was then validated. We identified a new risk stratification model based on clinical factors associated with (i) positive semen culture and (ii) prostate cancer (PCa) and bladder cancer (BC). Diagnostic accuracy of the two predictive models (EAU vs New) was assessed and decision curve analyses (DCA) tested their clinical benefit.Overall, 259 (91.5%) were high-risk and 24 (8.5%) low risk according to the EAU guidelines. Recurrent haemospermia was reported by 134 (47.4%) patients. 126 (44.5%) had baseline CCI score ≥ 1. At MVA logistic regression analysis, history of recurrent genito - urinary tract infections was identified as a predictor for positive semen culture (OR: 3.39, 95% CI: 1.77 - 6.57, P =.002). Likewise, baseline CCI ≥ 1 was identified as a predictor for PCa and BC (OR: 1.55, 95% CI: 1.17 - 2.04, P =.009). Sensitivity, specificity, and AUC of the EAU guidelines were 13.3%, 89.2% and 51% respectively, whereas the new model performed substantially better: 98.9%, 58% and 78% respectively.The application of the EAU guidelines risk stratification does not ensure proper identification of high-risk patients complaining of haemospermia. We propose a novel, better performing and easily implementable risk stratification tool.

Background: A severe male infertility factor has been associated with both lower health status and increased mortality in infertile men. Objectives: To investigate reproductive factors associated with health status impairment in infertile men over a 10-year time frame since the first clinical evaluation. Materials and methods: Data from 899 infertile men were analysed at baseline between 2003 and 2010. Health-significant comorbidities were scored with the Charlson Comorbidity Index. Patients were followed up yearly recording any worsening in their health status until 2019. Cox regression models were used to estimate hazard ratios and 95% confidence intervals of Charlson Comorbidity Index score increase. Results: At a median follow-up of 136 months (Interquartile range: 121, 156), 85 men (9.5%) depicted an increase of their baseline Charlson Comorbidity Index score of at least one point. The most frequent reason for Charlson Comorbidity Index upgrade was cancer (34%), cardiovascular diseases (29%) and diabetes mellitus (22%). Compared to patients without a Charlson Comorbidity Index increase, patients with a Charlson Comorbidity Index increase presented with higher body mass index and follicle-stimulating hormone values, a higher rate of baseline Charlson Comorbidity Index ≥ 1 (all p&nbsp

Testicular volume (TV) is considered a good clinical marker of hormonal and spermatogenic function. Accurate reference values for TV measures in infertile and fertile men are lacking. We aimed to assess references values for TV in white-European infertile men and fertile controls. We analyzed clinical and laboratory data from 1940 (95.0%) infertile men and 102 (5.0%) fertile controls. Groups were matched by age using propensity score weighting. TV was assessed using a Prader orchidometer (PO). Circulating hormones and semen parameters were investigated in every male. Descriptive statistics, Spearman's correlation, and logistic regression models tested potential associations between PO-estimated TV values and clinical variables. Receiver operating characteristic (ROC) curves were used to find TV value cutoffs for oligoasthenoteratozoospermia (OAT) and nonobstructive azoospermia (NOA) status in infertile men. The median testicular volume was smaller in infertile than that of fertile men (15.0 ml vs 22.5 ml; P < 0.001). TV positively correlated with total testosterone, sperm concentration, and progressive sperm motility (all P ≤ 0.001) in infertile men. At multivariable logistic regression analysis, infertile status (P < 0.001) and the presence of left varicocele (P < 0.001) were associated with TV < 15 ml. Testicular volume thresholds of 15 ml and 12 ml had a good predictive ability for detecting OAT and NOA status, respectively. In conclusion, infertile men have smaller testicular volume than fertile controls. TV positively correlated with total testosterone, sperm concentration, and progressive motility in infertile men, which was not the case in the age-matched fertile counterparts.

Background: Infertile men are at greater risk for oncological and nononcological chronic disease than fertile individuals. Objective: To investigate prostate-specific antigen (PSA) values in men presenting for primary couple's infertility compared with a cohort of fertile individuals, according to the recommendation of the European Association of Urology guidelines that a first PSA assessment should be done at 40–45 yr of age. Design, setting, and participants: This is a cross-sectional study. Data from 956 (90%) infertile men and 102 (9.6%) fertile participants were analysed. Circulating hormones, total PSA, and semen parameters were investigated in every man. Outcome measurements and statistical analysis: Descriptive statistics, local polynomial smoothing, and linear regression models were used to test potential associations with PSA levels. Results and limitations: Overall, PSA >1 ng/ml was found in 318 (30%) men. Serum PSA was higher (p = 0.02), while serum testosterone (p < 0.01) was lower in infertile than in fertile men. In participants younger than 40 yr, 176 (27%) men had PSA >1 ng/ml; of them, a greater proportion were infertile (28% infertile vs 17% fertile, p = 0.03). At multivariable linear regression analysis, infertile status (coefficient 0.21; 95% confidence interval 0.02–0.39) was associated with higher PSA values, after adjusting for age and serum testosterone level. This was a single-centre study, raising the possibility of selection biases. Conclusions: Infertile men have higher PSA values than fertile individuals. Of all, almost one out of three primary infertile men younger than 40 yr has a first total PSA value of >1 ng/ml. Patient summary: In this study, we observed that (1) infertile men have higher prostate-specific antigen (PSA) values than fertile individuals and (2) a greater proportion of infertile men younger than 40 yr had total PSA >1 ng/ml at the first assessment. These data might be relevant to study the potential clinical impact of more rigorous screening in primary infertile men. Infertile men have higher prostate-specific antigen (PSA) values than fertile individuals. One out of three infertile men younger than 40 yr has a first total PSA value of >1 ng/ml. Serum PSA is related to worse semen quality in infertile men.

Erectile dysfunction aetiology has been historically identified as organic, psychogenic and mixed.To stratify and compare a cohort of patients seeking medical help for erectile dysfunction for the first time according to the newly proposed binary classification of the European Association of Urology guidelines: 'primary organic' versus 'primary psychogenic'.Complete data from 2009 consecutive patients presenting for erectile dysfunction were analysed. All patients completed the International Index of Erectile Function at baseline. According to the presence of erectile dysfunction-related risk factors indexed by the European Association of Urology Guidelines on Sexual and Reproductive Health, patients were categorised as having primary organic (≥1 risk factor) or primary psychogenic (0 risk factor) erectile dysfunction. Descriptive statistics compared the two groups. Linear regression analysis tested the association between the number of risk factors and erectile dysfunction severity. Locally estimated scatterplot smoothing method graphically explored the relationship between the number of risk factors for erectile dysfunction and the International Index of Erectile Function domain scores.Median (interquartile range) age at first presentation was 50 (39-61) years. Of all, 1632 (86.2%) and 377 (13.8%) were identified as having primary organic and primary psychogenic erectile dysfunction, respectively. Overall, 1488 (74.1%) patients were40 years of age; in this subgroup, the most frequent risk factors were age, hypertension (29%), active smoking (42%) and alcohol intake (25.1%). Median (interquartile range) International Index of Erectile Function-erectile function score was 15 (7-22). Primary organic erectile dysfunction patients depicted lower International Index of Erectile Function-sexual desire and International Index of Erectile Function-orgasmic function scores (all p ≤ 0.02), whilst groups did not differ in terms of International Index of Erectile Function-erectile function, International Index of Erectile Function-intercourse satisfaction and International Index of Erectile Function-overall satisfaction scores.One out of nine patients complaining of erectile dysfunction depict criteria for primary psychogenic erectile dysfunction. Erectile function severity could be as severe as patients with organic erectile dysfunction. The single-centre-based cross-sectional nature of the study, raising the possibility of selection biases, is our main limitation.One out of nine patients presenting for erectile dysfunction depict criteria suggestive for primary psychogenic erectile dysfunction in the real-life setting. Patients with primary psychogenic and primary organic erectile dysfunction have comparable erectile dysfunction severity, thus outlining the importance of a comprehensive and tailored management work-up in every patient seeking medical help for the first time.

Objective: We aimed to test the association between age, BMI and sex-hormone–binding globulin (SHBG) in a homogenous cohort of white-European men presenting for primary couple’s infertility. Design: Retrospective study. Methods: Data from 1547 infertile men were analysed. Health-significant comorbidities were scored with the Charlson comorbidity index (CCI). Fasting serum hormones were measured in every patient. Age was considered according to quartile groups (41 years) and BMI as normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) and obesity (>30 kg/m2). Descriptive statistics and linear regression analysis tested the associations between age, BMI and SHBG. Results: Median SHBG levels increased across quartiles of age and decreased along with BMI increases (all P P P Conclusions: We found a wide distribution of SHBG concentrations across age and BMI values in primary infertile men. The association between BMI and lowered SHBG levels seems to be greater than the association of ageing with increased SHBG.

To describe the perioperative safety, functional and immediate post-operative oncological outcomes of minimally invasive RPLND (miRPLND) for testis cancer.We performed a retrospective multi-centre cohort study on testis cancer patients treated with miRPLND from 16 institutions in eight countries. We measured clinician-reported outcomes stratified by indication. We performed logistic regression to identify predictors for maintained postoperative ejaculatory function.Data for 457 men undergoing miRPLND were studied. miRPLND comprised laparoscopic (n = 56) or robotic (n = 401) miRPLND. Indications included pre-chemotherapy in 305 and post-chemotherapy in 152 men. The median retroperitoneal mass size was 32 mm and operative time 270 min. Intraoperative complications occurred in 20 (4%) and postoperative complications in 26 (6%). In multivariable regression, nerve sparing, and template resection improved ejaculatory function significantly (template vs bilateral resection [odds ratio (OR) 19.4, 95% confidence interval (CI) 6.5-75.6], nerve sparing vs non-nerve sparing [OR 5.9, 95% CI 2.3-16.1]). In 91 men treated with primary RPLND, nerve sparing and template resection, normal postoperative ejaculation was reported in 96%. During a median follow-up of 33 months, relapse was detected in 39 (9%) of which one with port site ( 1%), one with peritoneal recurrence and 10 (2%) with retroperitoneum recurrences.The low proportion of complications or peritoneal recurrences and high proportion of men with normal postoperative ejaculatory function supports further miRPLND studies.

INTRODUCTION AND OBJECTIVE:The European Urology Association (EAU) guidelines strongly suggest the use of integrated prognostic systems to assess oncologic outcomes after surgery in patients with lo...

INTRODUCTION AND OBJECTIVE:Current EAU Guidelines suggest that during the diagnostic work-up of an infertile man one semen analysis is sufficient in the case of normality as for WHO criteria. Conve...

INTRODUCTION AND OBJECTIVE:Experience (EXP) is a human factor that affects surgery: the relationship between surgical experience and clinical outcomes defines the learning curve of a procedure. Thu...

INTRODUCTION AND OBJECTIVE:Incidental detection of Small Renal Masses (SRMs) has been increasing due to the broad implementation of imaging exams. Numerous treatment approaches such as surgical int...

INTRODUCTION AND OBJECTIVE:Male factor infertility (MFI) is often associated with metabolic disorders such as diabetes mellitus and metabolic syndrome, where insulin resistance (IR) plays a relevan...

Study question Guidelines suggest that one semen analysis is sufficient during the diagnostic work-up of an infertile man in the case of normality as for WHO criteria. Summary answer We investigated the rate and the clinical features of men with abnormal sperm parameters at a second test, after a normal first semen analysis. What is known already A second test is recommended when the first semen analysis depicted abnormal sperm parameters. Study design, size, duration Complete demographic, clinical and laboratory data from 1358 consecutive primary infertile men (infertility as for WHO definition) were analysed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Serum hormones were measured in every patient. Patients underwent two consecutive semen analyses at the same laboratory, which followed 2010 WHO reference criteria. Participants/materials, setting, methods Descriptive statistics and logistic regression models tested the association between clinical variables and semen parameters. Receiver operative characteristic (ROC) curves were used to assess the relationship between clinical variables and to create a composite risk score for pathological sperm parameters at a second test. Main results and the role of chance At first analysis, 212 (15.6%) infertile men had normal semen parameters. Of 212, 87 (41.0%) had a second normal semen analysis, while 80 (37.7%), 35 (16.5%) and 10 (4.7%) men showed 1, 2 and 3 pathological sperm parameters at second test. Men with a pathological second semen analysis had higher CCI scores (p 6 mUI/ml and sperm concentration 0.8). Considering 1-point for each of the previous variables, the chances of a pathological second analysis increased from 38.8% to 74.6%, 77.3% and 100% among patients with risk scores of 0, 1, 2 and 3, respectively (p Limitations, reasons for caution It is a retrospective analysis at a single, tertiary-referral academic centre, thus raising the possibility of selection biases. In spite of this, all patients have been consistently analysed over time with a rigorous follow-up, thus limiting potential heterogeneity in terms of data reporting. Wider implications of the findings: Approximately 60% of infertile men with a normal semen analysis depicted a pathological second test. Smaller testicles, higher FSH, lower sperm concentrations were independently associated with a pathologic second test. These features could be useful to identify those infertile men with a normal semen analysis who deserve a second test. Trial registration number Not applicable

Study question Current scientific guidelines do not clearly suggest which patients would benefit the most from a sperm DNA fragmentation (SDF) test. Summary answer We aimed to investigate potential predictive factors for altered SDF in a homogenous cohort of white-European men presenting for primary couple’s infertility. What is known already High SDF has been associated with reduced fertilization rates, reduced chances of natural conception and an increased risk of early pregnancy loss. Study design, size, duration Data from 478 consecutive men with normal or altered SDF were analysed. Infertility was defined according to the WHO criteria. Semen analysis, SDF (according to SCSA) and serum hormones were measured in every patient. Health significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Altered SDF was considered with a threshold of > 30%. Participants/materials, setting, methods Descriptive statistics compared the overall characteristics of patients with normal SDF and altered SDF. Logistic regression analysis tested potential predictors of altered SDF. ROC curve was used to test the accuracy of the model in predicting SDF alteration Main results and the role of chance Of 478 patients, 253 (57.7%) had altered SDF. Median (IQR) age and BMI of the whole cohort were 38 (35-42) years and 25.1 (23.3-27.1) kg/m2 respectively. Patients with altered SDF were older (median (IQR) age: 39 (36-43) vs. 37 (34-38) years, p 35 years (OR: 2.45, p = 0.0009), FSH > 8.0 mIU/mL (OR: 2.23, p Limitations, reasons for caution It is a retrospective analysis at a single, tertiary-referral academic centre, thus raising the possibility of selection biases. In spite of this, all patients have been consistently analysed over time with a rigorous follow-up, thus limiting potential heterogeneity in terms of data reporting Wider implications of the findings Primary infertile men older than 35 years, with high serum FSH and low TMSC at baseline are the ones who mostly deserve a SDF test over their diagnostic work-up and that would potentially benefit the most of certain treatments to improve SDF value, thus increasing chances of conceiving. Trial registration number Not applicable

Study question We investigated the prevalence of kidney function impairment in a homogeneous cohort of white-European primary infertile men. Summary answer Mild kidney function impairment characteristics were found in 9% of asymptomatic and unaware patients presenting for primary infertility investigation. What is known already Infertile men have shown a worse overall health status compared to the fertile counterpart. We investigated the prevalence of kidney function impairment in a homogeneous cohort of white-European primary infertile men. Study design, size, duration In this corss-sectional study, complete clinical and laboratories data from a cohort of 557 consecutive men aged >18 years, presenting for primary infertility investigation were analyzed. Participants/materials, setting, methods Comorbidities (as scored with the Charlson Comorbidity Index (CCI)) were collected in each patient. Primary outcome was the presence of functional impairment of the kidney (defined as an estimated glomerular filtration rates Main results and the role of chance Of 557, 51 (9.3%) patients depicted at least a mild loss of kidney function (eGFR 0.05), after accounting for age, CCI, BMI, FSH, testicular volume, and varicocele. Limitations, reasons for caution Mild kidney function impairment characteristics were found in 9% of asymptomatic and unaware patients presenting for primary infertility investigation. Age and the rate of comorbidities are associated with reduced eGFR. Wider implications of the findings: This novel finding confirms growing data on a significant association of male infertility with a poorer overall male health status. Trial registration number Not applicable

Study question We aimed to investigate the rate of and the clinical characteristics of men with idiopathic versus unexplained infertility from a cohort of white-European men. Summary answer Approximately 20% and 5% of men evaluated for primary couple’s infertility depicted characteristics suggestive for idiopathic and unexplained infertility, respectively. What is known already Male factor infertility (MFI) can be associated with clinical, hormonal and genetic diseases, but MFI is idiopathic in almost 30% of cases. Study design, size, duration Data from 3098 infertile men (according to WHO definition) consecutively evaluated between 2003-2020 at a single academic centre were analysed and compared with those of 103 fertile controls. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Idiopathic infertility was defined for pathological semen analysis but normal physical examination and endocrine, genetic and biochemical laboratory testing. Unexplained infertility is defined as infertility of unknown origin with normal sperm parameters. Participants/materials, setting, methods Testicular volume (TV) was assessed with a Prader’s orchidometer. Serum hormones and sperm DNA fragmentation index (SDF) were measured in every patient. Vitamin D3 (VitD) deficiency was considered for vitD levels Main results and the role of chance Overall, 570 (18.5%) and 154 (5.0%) patients depicted criteria suggestive for either idiopathic or unexplained primary infertility, respectively. Groups were similar in terms of age, BMI, CCI, recreational habits, circulating serum hormones and SDF. Testicular volume was lower in men with idiopathic vs. unexplained infertility [median (IQR) 20 (15-25) vs. 20 (17-25); p Limitations, reasons for caution The small number of fertile controls may raise the possibility of biases. Wider implications of the findings Idiopathic and unexplained infertility were identified in approximately 20% and 5% of men evaluated, respectively. Idiopathic infertile men showed lower TV and lower vitD values compared to men with unexplained infertility. Future studies are needed to develop a more tailored management to these difficult MFI cases. Trial registration number .

Highlights • Prostate specific antigen is the standard circulating biomarker for prostate cancer. • We provide novel evidence that collagen 1 is an additional substrate for PSA. • PSA hampers first steps of cancer invasion. • Tissue-related PSA content/activity is inversely correlated to tumor progression. • Tissue-related PSA levels improve prediction of prostate cancer specific mortality., Aim Since its discovery Prostate Specific Antigen (PSA), also referred to as kallikrein-3 (KLK3), has been used as standard circulating biomarker for prostate cancer (PCa). However, its specificity remains not adequate and its mechanism of action still elusive. Therefore, deciphering PSA role throughout PCa-pathobiology would be relevant in improving both cancer diagnosis and outcome prediction. We investigated the possible role played by PSA on/in the tumor microenvironment and over the first steps of cancer invasion. Methods Fresh PCa-specimens and cell lines were used for ex-vivo/in-vitro invasion assays and assessment of prostate tissue-PSA (tPSA), type 1 collagen (COL1A1) and ß1-integrin expression. Tissue Cancer Genome Atlas (TCGA) and Decipher® datasets were considered to estimate tPSA clinical relevance. Results A more precise, inverse, correspondence between tPSA and clinical/pathological parameters was found than for circulating PSA. KLK3 combined with Gleason grade and pathologic stage, better predicted cancer-related mortality. Consistently, we demonstrated that PSA inhibits prostate extracellular-matrix (ECM) invasion by PCa cells. As for the mechanism of action, we provided novel information that PSA is able to cleave COL1A1, a main component of the ECM. Finally, ß1-integrin, a crucial COL1A1 transducing-receptor involved in tumor adhesion/invasion, resulted to be downregulated in PCa specimens with higher levels of tPSA. Conclusions By interfering with type 1 collagen and its downstream targets, PSA may hamper adhesion and path of the cancer cells through ECM and their migration ability, thus explaining the inverse correlation highlighted between prostate tPSA levels and clinically significant disease.

We assessed the concomitant impact of cigarette smoking and alcohol consumption in men presenting for primary couple's infertility. Data from 189 infertile men were analyzed. Semen analysis, serum hormones, and sperm DNA fragmentation (SDF) were obtained. Smoking status was categorized as follows: current nonsmoker (-S), moderate smoker (+MS), and heavy smoker (+HS). Alcohol consumption was categorized as follows: abstainer (-D), moderate drinker (+MD), and heavy drinker (+HD). Descriptive statistics and logistic regression models were applied. Among all the participants, 132 (69.8%), 30 (15.9%), and 27 (14.3%) patients were -S, +MS, and +HS, respectively. In addition, 67 (35.4%), 77 (40.7%) and 45 (23.8%) men were -D, +MD and +HD, respectively. Regarding concomitant habits, 52 (27.5%) patients were nonsmokers and abstainers (-S/-D: Group 1), 91 (48.1%) had at least one recreational habit (-S/+D or +S/-D: Group 2), and 46 (24.3%) were both smokers and drinkers (+S/+D: Group 3). Sperm concentration and progressive motility were lower in +HS and +HD, compared with -S and -D (all P < 0.05), respectively. Similarly, both parameters were significantly lower in Group 3 than Groups 1 and 2 (all P < 0.05). SDF values were higher in Group 3 than Groups 1 and 2 (both P < 0.05). In multivariate analysis, follicle-stimulating hormone (FSH) levels and concomitant +S/+D status were independent predictors of impaired sperm concentration and progressive motility (all P < 0.05). Heavy smoking and heavy drinking were associated with worse seminal parameters than moderate smoking/drinking and nonsmoking/abstaining. When concomitant, +S/+D status has an even greater detrimental effect on semen parameters.